Exploring T Cell Reactivity to Gliadin in Young Children with Newly Diagnosed Celiac Disease

[摘要] Class II major histocompatibility molecules confer disease risk in Celiac disease (CD) by presenting gliadin peptides to CD4 T cells in the small intestine.Deamidation of gliadin peptides by tissue transglutaminase creates immunogenic peptides presented by HLA-DQ2 and DQ8 molecules to activate proinflammatory CD4 T cells. Detecting gliadin specific T cell responses from the peripheral blood has been challenging due to low circulating frequencies and heterogeneity in response to gliadin epitopes.We investigated the peripheral T cell responses to alpha and gamma gliadin epitopes in young children with newly diagnosed and untreated CD.Using peptide/MHC recombinant protein constructs, we are able to robustly stimulate CD4 T cell clones previously derived from intestinal biopsies of CD patients.These recombinant proteins and a panel ofα- andγ-gliadin peptides were used to assess T cell responses from the peripheral blood.Proliferation assays using peripheral blood mononuclear cells revealed more CD4 T cell responses toα-gliadin thanγ-gliadin peptides with a single deamidatedα-gliadin peptide able to identify 60% of CD children.We conclude that it is possible to detect T cell responses without a gluten challenge or in vitro stimulus other than antigen, when measuring proliferative responses.

[学科分类] 内科医学